Dejex

Deferasirox

Chronic Fe overload in patients ≥2 yr caused by blood transfusions (transfusional hemosiderosis). Non-transfusion-dependent thalassemia syndromes in patients ≥10 yr.

Transfusional Fe overload Initially 20 mg/kg once daily. Patients receiving >14 mL/kg/mth of packed RBC & for reduction of Fe overload Initially 30 mg/kg daily. Patients receiving <7 mL/kg/mth of packed RBC & for maintenance of body Fe level Initially 10 mg/kg daily. Patients already well-managed on treatment w/ deferoxamine Starting dose should be numerically ½ of deferoxamine dose. Dose adjustment: 5-10 mg/kg. Patients not adequately controlled w/ 30 mg/kg/day & w/ serum ferritin levels persistently >2,500 mcg/L not decreasing over time Up to 40 mg/kg daily. Non-transfusion-dependent thalassemia syndromes Initially 10 mg/kg once daily. Dose adjustment: Patient w/ liver Fe conc (LIC) ≥7 mg Fe/g dry wt or serum ferritin >2,000 mcg/L Increase dose in 5-10 mg/kg increments. Patients in whom LIC is <7 mg Fe/g dry wt & was not assessed & serum ferritin ≤2,000 mcg/L Not >10 mg/kg. Moderate hepatic impairment (Child-Pugh class B) Reduce dose by 50%.

Should be taken on an empty stomach: Take at least 30 min before meals preferably at the same time daily. Disperse tab completely by stirring in 100-200 mL of water/apple juice/orange juice until a fine susp is obtained; consume entire content. Rinse the glass w/ a little water/juice to resuspend any residue & drink remainder. Do not disperse tab in fizzy drinks/milk. Do not chew/ break/crush tab or swallow whole. Do not take w/ Al-containing antacids.

Hypersensitivity. CrCl <40 mL/min or serum creatinine >2x the age-appropriate ULN. High-risk myelodysplastic syndrome patients. Patients w/ other hematological & non-hematological malignancies who are not expected to benefit from chelation therapy due to rapid disease progression.

Discontinue in case of serious hypersensitivity reactions; in suspected SJS; appearance of severe rash. Interrupt treatment if progressive increase in serum creatinine beyond ULN; decreased hearing & lens opacities occurs; in patient who develop unexplained cytopenia. Patients w/ CrCl between 40-60 mL/min. Patients who develop diarrhea or vomiting. Liver cirrhosis & multi-organ failure; upper GI ulceration & haemorrhage; ulcers complicated w/ GI perforation. Risk of toxicity in patients w/ low Fe burden or slightly elevated serum ferritin levels. Reduce dose by 10 mg/kg if non-progressive rise in serum creatinine by >33% above the average in adult patient; 10 mg/kg if serum creatinine levels rise above the age-appropriate ULN at 2 consecutive visits in ped patient. Assess serum creatinine &/or CrCl prior to therapy & monitor mthly thereafter in patient w/ acute renal failure. Wkly monitoring of serum creatinine &/or CrCl in 1st mth after initiation or modification of therapy, & mthly thereafter in patient w/ pre-existing renal conditions. Monitor serum transaminases, bilirubin & alkaline phosphatase prior to initiation of treatment, every 2 wk during 1st mth & mthly thereafter; blood counts regularly; body wt & longitudinal growth in ped patient at regular interval (every 12 mth). Galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption. Combination w/ drugs known to have ulcerogenic potential eg, NSAIDs, corticosteroids, or oral bisphosphonates; Fe chelator therapies. May affect ability to drive & use machines. Not recommended in patients w/ severe hepatic impairment (Child-Pugh Class C). Not to be used during pregnancy. Not recommended during lactation. Renal tubulopathy in childn w/ β-thalassemia & adolescents w/ serum ferritin <1,500 mcg/L. Growth retardation in childn. Elderly who had advanced hematologic malignancies &/or low platelet counts.

Increased blood creatinine. Headache; diarrhea, constipation, vomiting, nausea, abdominal pain & distension, dyspepsia; increased transaminases; rash, pruritus; proteinuria. SJS.

Decreased systemic exposure w/ potent UGT inducer eg, rifampicin, phenytoin, phenobarb, ritonavir. Decreased midazolam exposure. Concomitant use w/ substances metabolized through CYP3A4 eg, ciclosporin, simvastatin, hormonal contraceptives; other CYP2C8 substrates eg, paclitaxel; CYP1A2 substrates. Increased repaglinide AUC & C_max. Increased theophylline AUC. Decreased effectiveness w/ Al oxide. NSAIDs, corticosteroids or oral bisphosphonates.

Antidotes & Detoxifying Agents

V03AC03 - deferasirox ; Belongs to the class of iron chelating agents. Used in the management of chronic iron overload associated with blood transfusion.

S